Corticosteroids also referred as glucocorticosteroids, glucocorticoids or just steroids influence different body tissues and produce effects on various responsive cells.
Corticosteroids have been found to possess anti-inflammatory and immunosuppressive properties. Several Corticosteroids such as Flunisolide, Fluocinolone acetonide and Fluocinonide are used for treatment of several disorders.
Corticosteroids with significant structural changes and chemical manipulation have been developed. In general, therapeutic corticosteroids have a 21-carbon steroid skeleton; Modifications to this skeleton selectively alter the degree of anti-inflammatory activity and the metabolic consequences and vary the duration of activity and protein-binding affinity of the resultant compound.
Therapeutic corticosteroids are typically classified based on their relative glucocorticoid and mineralocorticoid potency. Such as, acetonides at C-16, C-17 are to improve potency of anti-inflammatory activity of steroids but possess low systematic activity.
Further, halogenations of steroids molecule by 9-halo or 6, 9 dihalo substitutions increase their systematic activity and enhances both glucocorticoid and mineralocorticoid activity of C-16, C-17 substituted acetals, ketals, acetonides, fused ring compounds. For example, Flunisolide is a topical corticosteroid having 6-fluoro and C-16, C-17 acetonide group.
The process for preparation of Corticosteroids having C-16, C-17 substituted acetals, ketals, acetonides, fused ring compounds and halogens at C-6, C-9 or both positions have been disclosed at different instances. However, most of these synthetic procedures involve 6 halo or 6, 9 dihalo, 16a, 17a diols or both as starting materials, which are compounds difficult to prepare handle and purify, the use of toxic solvents or long reaction times are ineffective for large scale synthesis.
For instance, U.S. Pat. No. 3,126,375 discloses a process for the preparation of 6 halo corticoids. The known methods for the preparation of pregnadiene 16, 17acetals, ketals involve the starting material as 6 halo or 6, 9 halo having 16a, 17a diols with aldehydes in the presence of catalyst such as copper sulphate or copper sulphate or perchloricacid solvent which are compounds difficult to prepare and purify and unstable and use of these solvents on large scale require specialized equipments.
WO 03/47329 discloses a method for the preparation of 6α-fluorinated corticosteroids. This application is specific to a 21 ester, 17-hydroxy corticosteroids and does not disclose the various chemicals, starting material, products or reactions and modification thereof. Therefore, the process is not repeatable.
Hence, there is a need to prepare novel Corticosteroidshalogenated at C-6, C-9 or both positions and C-16, C-17 acetals, ketals, acetonides, fused ring compounds using stable, easily available starting materials which can be easily purified, convenient, having high yields, industrially scalable and which does not involve the use of harmful solvents.